FunFOLDQA: a quality assessment tool for protein-ligand binding site residue predictions

The estimation of prediction quality is important because without quality measures, it is difficult to determine the usefulness of a prediction. Currently, methods for ligand binding site residue predictions are assessed in the function prediction category of the biennial Critical Assessment of Techniques for Protein Structure Prediction (CASP) experiment, utilizing the Matthews Correlation Coefficient (MCC) and Binding-site Distance Test (BDT) metrics. However, the assessment of ligand binding site predictions using such metrics requires the availability of solved structures with bound ligands. Thus, we have developed a ligand binding site quality assessment tool, FunFOLDQA, which utilizes protein feature analysis to predict ligand binding site quality prior to the experimental solution of the protein structures and their ligand interactions. The FunFOLDQA feature scores were combined using: simple linear combinations, multiple linear regression and a neural network. The neural network produced significantly better results for correlations to both the MCC and BDT scores, according to Kendall’s τ, Spearman’s ρ and Pearson’s r correlation coefficients, when tested on both the CASP8 and CASP9 datasets. The neural network also produced the largest Area Under the Curve score (AUC) when Receiver Operator Characteristic (ROC) analysis was undertaken for the CASP8 dataset. Furthermore, the FunFOLDQA algorithm incorporating the neural network, is shown to add value to FunFOLD, when both methods are employed in combination. This results in a statistically significant improvement over all of the best server methods, the FunFOLD method (6.43%), and one of the top manual groups (FN293) tested on the CASP8 dataset. The FunFOLDQA method was also found to be competitive with the top server methods when tested on the CASP9 dataset. To the best of our knowledge, FunFOLDQA is the first attempt to develop a method that can be used to assess ligand binding site prediction quality, in the absence of experimental data.

Nuclear fuel cycles: interfaces with the environment

The waste materials generated in the nuclear fuel cycle are very varied,ranging from the tailings arising from mining and processing uranium ore, depleted uranium in a range of chemical forms, to a range of process wastes of differing activities and properties. Indeed, the wastes generated are intimately linked to the options selected in operating the nuclear fuel cycle, most obviously to the management of spent fuel. An open fuel cycle implies the disposal of highly radioactive spent fuel, whereas a closed fuel cycle generates a complex array of waste streams. On the other hand, a closed fuel cycle offers options for waste management, for example reduction in highly active waste volume, decreased radiotoxicity, and removal of fissile material. Many technological options have been proposed or explored, and each brings its own particular mix of wastes and environmental challenges.

Understanding lake and catchment history as a tool for integrated lake management

Sustainable lake management for nutrient-enriched lakes must be underpinned by an understanding of both the functioning of the lake, and the origins of changes in nutrient loading from the catchment. To date, limnologists have tended to focus on studying the impact of nutrient enrichment on the lake biota, and the dynamics of nutrient cycling between the water column, biota and sediments within the lake. Relatively less attention has been paid to understanding the specific origins of nutrient loading from the catchment and nutrient transport pathways linking the lake to its catchment. As such, when devising catchment management strategies to reduce nutrient loading on enriched lakes, assumptions have been made regarding the relative significance of non-point versus point sources in the catchment. These are not always supported by research conducted on catchment nutrient dynamics in other fields of freshwater science. Studies on nutrient enrichment in lakes need to take account of the history of catchment use and management specific to each lake in order to devise targeted and sustainable management strategies to reduce nutrient loading to enriched lakes. Here a modelling approach which allows quantification of the relative contribution of nutrients from each specific point and non-point catchment source over the course of catchment history is presented. The approach has been applied to three contrasting catchments in the U.K. for the period 1931 to present. These are the catchment of Slapton Ley in south Devon, the River Esk in Cumbria and the Deben Estuary in Suffolk. Each catchment showed marked variations in the nature and intensity of land use and management. The model output quantifies the relative importance of point source versus non-point livestock and land use sources in each of the catchments, and demonstrates the necessity for an understanding of site-specific catchment history in devising suitable management strategies for the reduction of nutrient loading on enriched lakes.

The multisensory attentional consequences of tool use: a functional magnetic resonance imaging study

Background: Tool use in humans requires that multisensory information is integrated across different locations, from objects seen to be distant from the hand, but felt indirectly at the hand via the tool. We tested the hypothesis that using a simple tool to perceive vibrotactile stimuli results in the enhanced processing of visual stimuli presented at the distal, functional part of the tool. Such a finding would be consistent with a shift of spatial attention to the location where the tool is used. Methodology/Principal Findings: We tested this hypothesis by scanning healthy human participants' brains using functional magnetic resonance imaging, while they used a simple tool to discriminate between target vibrations, accompanied by congruent or incongruent visual distractors, on the same or opposite side to the tool. The attentional hypothesis was supported: BOLD response in occipital cortex, particularly in the right hemisphere lingual gyrus, varied significantly as a function of tool position, increasing contralaterally, and decreasing ipsilaterally to the tool. Furthermore, these modulations occurred despite the fact that participants were repeatedly instructed to ignore the visual stimuli, to respond only to the vibrotactile stimuli, and to maintain visual fixation centrally. In addition, the magnitude of multisensory (visual-vibrotactile) interactions in participants' behavioural responses significantly predicted the BOLD response in occipital cortical areas that were also modulated as a function of both visual stimulus position and tool position. Conclusions/Significance: These results show that using a simple tool to locate and to perceive vibrotactile stimuli is accompanied by a shift of spatial attention to the location where the functional part of the tool is used, resulting in enhanced processing of visual stimuli at that location, and decreased processing at other locations. This was most clearly observed in the right hemisphere lingual gyrus. Such modulations of visual processing may reflect the functional importance of visuospatial information during human tool use

An extratropical cyclone database: A tool for illustrating cyclone structure and evolution characteristics

Extratropical cyclone lifecycles have been studied extensively with the aim of understanding the dynamical mechanisms involved in their development. Previous work has often been based on subjective analysis of individual case studies. Such case studies have contributed heavily to the generation of conceptual models of extratropical cyclones that provide a framework for understanding the dynamical evolution of cyclones. These conceptual models are widely used in educational meteorology courses throughout the world to illustrate the basic structure and evolution of extratropical cyclones. This article presents a database of extratropical cyclone composites which highlight the average structure and evolution of 20 years of extratropical cyclones, as opposed to individual case studies. The composite fields are achieved by combining a database containing cyclone tracks from the ERA-Interim reanalysis (1989-2009, 6 hourly) with the full 3D ERA-Interim reanalysis fields. Vertical and horizontal composites of cyclone structure for cyclones generated in the Atlantic and Pacific regions identifying features such as the relative positions of cold, warm and occluded fronts and their associated wind and cloud patterns are shown. In addition the evolution of cyclonic flows such as the warm and cold conveyor belts and dry intrusion are illustrated. A webpage containing an archive of the composited data is freely available for educational purposes.

The National Audit Office uses OR to assess the value for money of public services

Supreme audit institutions (SAIs) have an important role in assessing value for money in the delivery of public services. Assessing value for money necessarily involves assessing counterfactuals: good value for money has been achieved if a policy could not reasonably have been delivered more efficiently, effectively, or economically. Operations research modelling has the potential to help in the assessment of these counterfactuals. However, is such modelling too arcane, complex, and technically burdensome for organisations that, like SAIs, operate in a time- and resource-constrained and politically charged environment? We report on three applications of modelling at the UK's SAI, the National Audit Office, in the context of studies on demand management in tax collection, end-of-life care, and health-care associated infections. In all cases, the models have featured in the audit reports and helped study teams come to a value-for-money judgment. We conclude that OR modelling is indeed a valuable addition to the value-for-money auditor's methodological tool box.

The Köppen climate classification as a diagnostic tool for general circulation models

Koppen climate classification was applied to the output of atmospheric general circulation models and coupled atmosphere-ocean circulation models. The classification was used to validate model control runs of the present climate and to analyse greenhouse gas warming simulations The most prominent results of the global warming con~putationsw ere a retreat of regions of permafrost and the increase of areas with tropical rainy climates and dry climates.

Knowledge Interfaces and Practices of Negotiation: Cases from a Women's Group in Bolivia and an Oil Refinery in Wales

This chapter examines encounters between international institutions that frame their objectives through a global policy language, and people whose lives are the focus for change heralded by these institutions. It explores how a global policy language, which seeks consensus and equality, can be at odds with local understandings, conflict and intentions.

Haptic interfaces: the live and the recorded body in Beckett's Eh Joe on stage and screen

Beckett’s sparse and minimalist pieces have continuously addressed the nature and characteristics of the media for which they were written. What does it mean when a work written specifically for television is transposed to the stage, as film director Atom Egoyan did in his 2006 version of Beckett’s Eh Joe? This article will focus on the implications of such a transposition and discuss how Egoyan’s version reveals the haptic interface present in the original piece, between body and technology, between the flesh and “spirit made light” of the electronic broadcast.

Scattering of electromagnetic waves by rough interfaces and inhomogeneous layers

We consider a two-dimensional problem of scattering of a time-harmonic electromagnetic plane wave by an infinite inhomogeneous conducting or dielectric layer at the interface between semi-infinite homogeneous dielectric half-spaces. The magnetic permeability is assumed to be a fixed positive constant. The material properties of the media are characterized completely by an index of refraction, which is a bounded measurable function in the layer and takes positive constant values above and below the layer, corresponding to the homogeneous dielectric media. In this paper, we examine only the transverse magnetic (TM) polarization case. A radiation condition appropriate for scattering by infinite rough surfaces is introduced, a generalization of the Rayleigh expansion condition for diffraction gratings. With the help of the radiation condition the problem is reformulated as an equivalent mixed system of boundary and domain integral equations, consisting of second-kind integral equations over the layer and interfaces within the layer. Assumptions on the variation of the index of refraction in the layer are then imposed which prove to be sufficient, together with the radiation condition, to prove uniqueness of solution and nonexistence of guided wave modes. Recent, general results on the solvability of systems of second kind integral equations on unbounded domains establish existence of solution and continuous dependence in a weighted norm of the solution on the given data. The results obtained apply to the case of scattering by a rough interface between two dielectric media and to many other practical configurations.

The Empirical Forcing Function as a tool for the diagnosis of large-scale atmospheric anomalies

The time-mean quasi-geostrophic potential vorticity equation of the atmospheric flow on isobaric surfaces can explicitly include an atmospheric (internal) forcing term of the stationary-eddy flow. In fact, neglecting some non-linear terms in this equation, this forcing can be mathematically expressed as a single function, called Empirical Forcing Function (EFF), which is equal to the material derivative of the time-mean potential vorticity. Furthermore, the EFF can be decomposed as a sum of seven components, each one representing a forcing mechanism of different nature. These mechanisms include diabatic components associated with the radiative forcing, latent heat release and frictional dissipation, and components related to transient eddy transports of heat and momentum. All these factors quantify the role of the transient eddies in forcing the atmospheric circulation. In order to assess the relevance of the EFF in diagnosing large-scale anomalies in the atmospheric circulation, the relationship between the EFF and the occurrence of strong North Atlantic ridges over the Eastern North Atlantic is analyzed, which are often precursors of severe droughts over Western Iberia. For such events, the EFF pattern depicts a clear dipolar structure over the North Atlantic; cyclonic (anticyclonic) forcing of potential vorticity is found upstream (downstream) of the anomalously strong ridges. Results also show that the most significant components are related to the diabatic processes. Lastly, these results highlight the relevance of the EFF in diagnosing large-scale anomalies, also providing some insight into their interaction with different physical mechanisms.

DK-1D: a drift-kinetic simulation tool for modelling the shear Alfvén wave and its interaction with collisionless plasma

We present a highly accurate tool for the simulation of shear Alfven waves (SAW) in collisionless plasma. SAW are important in space plasma environments because for small perpendicular scale lengths they can support an electric field parallel to the ambient magnetic field. Electrons can be accelerated by the parallel electric field and these waves have been implicated as the source of vibrant auroral displays. However, the parallel electric field carried by SAW is small in comparison to the perpendicular electric field of the wave, making it difficult to measure directly in the laboratory, or by satellites in the near-Earth plasma environment. In this paper, we present a simulation code that provides a means to study in detail the SAW-particle interaction in both space and laboratory plasma. Using idealised, small-amplitude propagating waves with a single perpendicular wavenumber, the simulation code accurately reproduces the damping rates and parallel electric field amplitudes predicted by linear theory for varying temperatures and perpendicular scale lengths. We present a rigorous kinetic derivation of the parallel electric field strength for small-amplitude SAW and show that commonly-used inertial and kinetic approximations are valid except for where the ratio of thermal to Alfv\'{e}n speed is between 0.7 and 1.0. We also present nonlinear simulations of large-amplitude waves and show that in cases of strong damping, the damping rates and parallel electric field strength deviate from linear predictions when wave energies are greater than only a few percent of the plasma kinetic energy, a situation which is often observed in the magnetosphere. The drift-kinetic code provides reliable, testable predictions of the parallel electric field strength which can be investigated directly in the laboratory, and will help to bridge the gap between studies of SAW in man-made and naturally occuring plasma.

Linguistic interfaces and language acquisition in childhood: introduction to the special issue

Much contemporary L1 acquisition theory and empirical research are guided by the hypothesis that acquisition delays in children are often related to the integration of information across grammatical and other cognitive modules, such as syntax and discourse-pragmatics (see e.g., Grinstead, 2010). This special issue brings together cutting edge research from all relevant paradigms addressing interface issues in child language acquisition and provides a platform for the study of the interaction between different levels of linguistic knowledge. In this introduction, we present the reader with the tools needed to best understand the contributions of the individual studies and what they bring to bear on larger theoretical questions as a collective.